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Topic 8 – Motor Neuron Disorders

& Spinal Cord Injury

1. Terminology
2. "Upper motor neuron" injury
3. Mechanisms of damage
4. Some disorders

Motor System Disorders -


Terminology
• Muscle Strength
• Paralysis / Paresis
• hemi-, para- , or tetra (quad)-
plegia

• Muscle Bulk
• atrophy – disuse or neurogenic

Motor System Disorders -


Terminology
• Upper motor neurons
• Originate in "higher" regions of
brain such as motor cortex
• Corticospinal tract

• Lower motor neurons


• Directly innervate skeletal
muscles
Motor System Disorders -
Terminology
• Hypotonia - abnormally low
resistance to stretch
• cerebellar disorders
• LMN lesions
• acute UMN lesions

• Hypertonia - abnormally strong


resistance to stretch
• chronic UMN lesions
• 2 types = spastic and rigid

Motor System Disorders -


Terminology
• Spastic Hypertonia
• resistance to passive movement
is velocity sensitive

• Rigidity
• resistance to passive movement
remains constant regardless of
velocity
• Decorticate / Decerebrate

Decerebrate Rigidity
Decerebrate -
upper brainstem
or lower
midbrain

Source: Haines, Fundamental


Neuroscience, Churchill-Livingstone,
2002

Decorticate Rigidity

Decorticate -
severe
lesion
superior to
midbrain

Source: Haines, Fundamental


Neuroscience, Churchill-Livingstone,
2002
Topic 8 – Motor Neuron Disorders
& Spinal Cord Injury

1. Terminology
2. "Upper motor neuron" injury
3. Mechanisms of damage
4. Some disorders

Overall muscle tone is


determined by
1. Intrinsic elastic properties of muscle
2. Neural input

Stretch reflex -

- contraction in response
to lengthening
- receptor is muscle
spindle (Ia afferent fiber)

- descending pathways
modify gain of reflex

Source: Kandel et al., Principles of Neural Science, McGraw Hill, 2000


Hoffmann Reflex

- stimulate
Ia afferents
(and motor
neurons)

- measure
"M-wave"
and "H-
wave" using
EMG

Source: Kandel et al., Principles of Neural Science, McGraw Hill, 2000

"Spinal shock" -
• Complete absence of reflexes
• Maybe from sudden withdrawal of
descending input

• Reflexes recover (weeks – months) and


become oversensitive…

tactile stim. foot


"Hyperactive" reflexes
• ‘spasm-like' muscle
bursts in response to
mild stimuli
• loss of descending
inhibition
Increased resistance
to stretch -
• Velocity-dependent
hypertonia
Source: Latash, Neurophysiological Basis of Movement,
Human Kinetics, 1998.
Treatment -

- administration of baclofen to spinal cord


- GABA B receptor agonist
- inhibition of synapse between Ia fibers
and motor neurons

Babinski’s Sign
• stroking across plantar
surface of foot normally
causes flexion of toes

• Upper motor neuron


damage can reverse
this response

Source: Lundy-Ekman, Neuroscience: Fundamentals for Rehabilitation, Saunders, 2002

Summary of "UMN" Injury Effects

Source: Latash, Neurophysiological Basis of Movement, Human Kinetics, 1998.


Topic 8 – Motor Neuron Disorders
& Spinal Cord Injury

1. Terminology
2. "Upper motor neuron" injury
3. Mechanisms of damage
4. Some disorders

Primary Injury –
mechanical damage to neuronal
apparatus

Secondary Injury –
occurs over hours post-injury

Glutamate - Excitotoxicity
NMDA Receptor - GLU binds to R and
opens Na+ channels

- ↑ Na+, draws water


into the cell = edema

- ↑ Ca++ , activates
proteases, lipases that
degrade components
of cell, may initiate
apoptosis
Source: Kandel et al., Principles of Neural Science, McGraw Hill, 2000
Neuroprotective strategies

- block glutamate receptors

- antioxidants

- block Na+ channels

Na+ Channel Blockers


BBB = measure of locomotor function

Riluzole

Control

Weeks Post-Injury
Adapted from: Schwartz and Fehlings, J. Neurosurg., 2001, 94(Suppl 2):245-256.

Na+ Channel Blockers


• effects on integrity of descending
spinal tracts

Adapted from: Schwartz and Fehlings, J. Neurosurg., 2001, 94(Suppl 2):245-256.


Na+ Channel Blockers – Tissue Loss

Riluzole

Control

Source: Schwartz and Fehlings, J. Neurosurg., 2001, 94(Suppl 2):245-256.

Wallerian Degeneration
Axotomy - transection of the
axon by cutting or crushing
Can result in degeneration of pre- /
post-synaptic cells and glia.

Source: Kandel et al., Principles of Neural Science, McGraw Hill, 2000

Wallerian Degeneration

Source: Kandel et al., Principles of Neural Science, McGraw Hill, 2000


Possible Therapies
• Regeneration of damaged axons

• Remyelination – Schwann cell


transplants

• Cell replacement – stem cells

• Restoring function: disruption of nerve pathway


– Unlike peripheral nerves, axons in the brain and spinal
cord cannot regenerate
• Therapeutic goal: regrowth, ‘bridge the gap’
– Prepare graft using peripheral helper cells (schwann)
• Still being tested on rats. No huge success yet (but getting there!)
Source: Miami Project to Cure Paralysis

• One problem this research is encountering is getting the


graft past the bridge and onto the spinal tissue
Source: Miami Project to Cure Paralysis
• Instead of patching disruption, a
second approach is to REPLACE
damaged nerves
– Use of fetal cells successful in
animal research

• Problem 3: Demyelination
– Also get with some spinal
cord injuries
– Again, trying to trigger
Remyelination using Schwann
cells from the periphery

Poliomyelitis

Loss of lower motor neuron cell bodies

• poliovirus
• acute infection of ventral horn of spinal cord
• Selectively destroys lower motor neurons –
denervates muscle
Source: Lundy-Ekman, Neuroscience: Fundamentals for Rehabilitation, Saunders, 2002

Poliomyelitis

Source: Lundy-Ekman, Neuroscience: Fundamentals for Rehabilitation, Saunders, 2002


Amyotrophic Lateral Sclerosis
(ALS)
- degeneration of "upper" and
"lower" motor neurons
- neurogenic atrophy of muscles
- correlated with mutation in
chromosome 21

Multiple Sclerosis

Source: Kandel et al., Principles of Neural Science, McGraw Hill, 2000

Axonal Conduction Block


• normally, voltage gated K+ channels
are present in the internodes and v-g
Na+ channels are densely packed in
region of node

• after demyelination, electrical


properties of axon change

• Conduction slows or may become


blocked